Synthesis of alkyl‐modified poly(sodium glutamate)s for preparation of polymer‐protein nanoparticles in combination with N,N,N‐trimethyl chitosan

The negatively charged, water‐soluble, hydrophobically modified poly(sodium glutamate)s containing different amounts of alkyl grafts were synthesized. First, poly(γ‐benzyl‐L‐glutamate) was prepared by ring‐opening polymerization of the corresponding N‐carboxyanhydride, which was in the next step aminolysed with octylamine. After removal of the remaining benzyl protective groups, the alkyl‐modified poly(sodium glutamate)s [P(Glu‐oa)] were obtained and, together with the oppositely charged N,N,N‐trimethyl chitosan (TMC), used for the preparation of nanoparticles (NPs) of a recombinant granulocyte colony‐stimulating factor (GCSF) protein by polyelectrolyte complexation method. It is observed that, beside electrostatic interaction, the hydrophobic grafts on poly(sodium glutamate)s significantly contribute to association efficiency (AE) with GCSF protein. The addition of TMC solution to the dispersion of GCSF/P(Glu‐oa) complexes results in formation of much more defined NPs with high AE and final protein loading. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2976–2985     

Biomimetic pH/redox dual stimuli‐responsive zwitterionic polymer block poly(L‐histidine) micelles for intracellular delivery of doxorubicin into tumor cells

A series of pH/redox dual stimuli‐responsive poly(2‐methacryloyloxyethyl phosphorylcholine)₂₅‐block‐poly(l ‐histidine)_n (p[MPC])₂₅‐b‐p[His]_n, n = 20, 35, 50, and 75) copolymers consisting of a pH‐responsive p(His)_n block and a biocompatible phospholipid analog p(MPC) block connected by a redox‐responsive disulfide linker have been synthesized. The block copolymers are self‐assembled into uniform micelles (～100 nm) in which doxorubicin (Dox) is efficiently encapsulated. The in vitro release profile shows an enhanced release of Dox at low pH (5.0) in 10 mM glutathione (GSH). The in vitro cell viability assays performed using various cell lines show that the blank hybrid micelles have no acute or intrinsic toxicity. A pH‐dependent cytotoxicity is observed with the Dox‐loaded micelles, especially at pH 5.0. Moreover, confocal microscopy images and flow cytometry results show the pH‐dependent cellular uptake of Dox‐loaded micelles. Therefore, the Dox‐loaded micelles can be considered a good candidate for cancer therapy. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2061–2070     

From Distinct Metallopeptoids to Self-Assembled Supramolecular Architectures

The construction of synthetic protein mimics is a central goal in chemistry. A known approach for achieving this goal is the self-assembly of synthetic biomimetic sequences into supramolecular structures. Obtaining different 3D structures via a simple sequence modification, however, is still challenging. Herein we present the design and synthesis of biomimetic architectures, via the self-assembly of distinct copper-peptoid duplexes. We demonstrate that changing only one non-coordinating side-chain within the peptoids—sequence-specific N-substituted glycine oligomers—leads to different supramolecular structures. Four peptoid trimers incorporating 2,2’-bipyridine and pyridine ligands, and a non-coordinating but rather a structure-directed bulky group were synthesized, and their solutions were treated with Cu²⁺ in a 1:1 ratio. Single-crystal X-ray analysis of the products revealed the self-assembly of each peptoid into a metallopeptoid duplex, followed by the self-assembly of multiple duplexes and their packing into a three-dimensional supramolecular architecture via hydrogen bonding and π–π interactions. Tuning the non-coordinating side-chain enables to regulate both the final structure being either a tightly packed helical rod or a nano-channel, and the pore width of the nano-channels. Importantly, all the metallopeptoids structures are stable in aqueous solution as verified by cryo-TEM measurements and supported by UV/Vis and EPR spectroscopies and by ESI-MS analysis. Thus, we could also demonstrate the selective recognition abilities of the nano-channels towards glycerol.     

A Porphyrin-Based Covalent Organic Framework for Metal-Free Photocatalytic Aerobic Oxidative Coupling of Amines

Imines are important intermediates in drug synthesis. Photocatalytic aerobic oxidative coupling of amines has been considered as a clean and promising way to produce imines and has attracted great attention. Herein, we designed and synthesized a novel two-dimensional porphyrin-based covalent organic framework (Por-BC-COF) which adopts an AA stacking mode with excellent crystallinity, high Brunauer–Emmett–Teller surface areas (1200 m² g⁻¹), wide light absorption range (200–1300 nm) and good stability in a variety of organic solvents. Por-BC-COF can be used as a metal-free heterogeneous photocatalyst for the photocatalytic oxidation of amines to imines under visible light and red light with a high yield (97 %). This work presents a novel and efficient COF photocatalyst in the application of light-driven organic synthesis.     

Confinement and controlled release of quinine on chitosan–montmorillonite bionanocomposites

To accomplish the controlled‐release systems based on layered clay minerals, one of the best ways is to intercalate organic molecules into the interlayer gallery of clay minerals. Into a series of chitosan (CS) intercalated montmorillonite (MMT) nanocomposites, prepared via ion‐exchange route, antimalarial drug [quinine (QUI)] was loaded to act as effective drug delivery systems. Among the CS–MMT nanocomposites, higher drug adsorption with decreasing CS concentration was observed. CS–MMT and CS–MMT/QUI intercalated compounds were characterized by powder X‐ray diffraction, Fourier transform infrared spectroscopy, and thermal analysis. The synthesized nanocomposites, filled in the gelatin capsules followed by coating of Eudragit® L 100, were tested for in vitro drug release performance in the sequential buffer environments at 37 ± 0.5 °C. As no drug release (0%) was observed in the gastric fluid, the coating of Eudragit® L 100 to the capsules is highly adequate. However, the drug release rate was comparatively faster from the CS intercalated clay with compare with pure clay. The drug release kinetic data revealed that the release of QUI from the nanocomposites can be explained by modified Freundlich model. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Amphiphilic gradient copolymers of 2‐methyl‐ and 2‐phenyl‐2‐oxazoline: self‐organization in aqueous media and drug encapsulation

Gradient (or pseudo‐diblock) copolymers were synthesized from 2‐methyl‐2‐oxazoline and 2‐phenyl‐2‐oxazoline monomer mixtures via cationic polymerization. The self‐assembling properties of these biocompatible gradient copolymers in aqueous solutions were investigated, in an effort to use the produced nanostructures as nanocarriers for hydrophobic pharmaceutical molecules. Dynamic and static light scattering as well as AFM measurements showed that the copolymers assemble in different supramolecular nanostructures (spherical micelles, vesicles and aggregates) depending on copolymer composition. Fluorescence spectroscopy studies revealed a microenvironment of unusually high polarity inside the nanostructures. This observation is related partly to the gradient structure of the copolymers. The polymeric nanostructures were stable with time. Their structural properties in different aqueous media—PBS buffer, RPMI solution—simulating conditions used in pharmacological/medicinal studies, have been also investigated and a composition dependent behavior was observed. Finally, the hydrophobic drug indomethacin was successfully encapsulated within the gradient copolymer nanostructures and the properties of the mixed aggregates were studied in respect to the initial copolymer assemblies. The produced aggregates encapsulating indomethacin showed a significant increase of their mass and size compared to original purely polymeric ones. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Continuum theory of swelling material surfaces with applications to thermo-responsive gel membranes and surface mass transport

Soft membranes are commonly employed in shape-morphing applications, where the material is programmed to achieve a target shape upon activation by an external trigger, and as coating layers that alter the surface characteristics of bulk materials, such as the properties of spreading and absorption of liquids. In particular, polymer gel membranes experience swelling or shrinking when their solvent content change, and the non-homogeneous swelling field may be exploited to control their shape. Here, we develop a theory of swelling material surfaces to model polymer gel membranes and demonstrate its features by numerically studying applications in the contexts of biomedicine, micro-motility, and coating technology. We also specialize the theory to thermo-responsive gels, which are made of polymers that change their affinity with a solvent when temperature varies.     

Higher-order time integration with a local Lax–Wendroff procedure for a central scheme on an overlapping grid

We have implemented a high-order Lax–Wendroff type time integration for a central scheme on an overlapping grid for conservation law problems. Using a local iterative approach presented by Dumbser et al. (JCP, 2008) [12], we extend a local high-order spatial reconstruction on each cell to a local higher-order space–time polynomial on the cell. We rewrite the central scheme in a fully discrete form to avoid volume integration in the space–time domain. The fluxes at cell interfaces are calculated directly via integrating a higher-order space–time reconstruction of the flux. We compare this approach with the corresponding multi-stage Runge–Kutta time integration (RK). Numerical results show that the new time integration is more cost-effective.